Abstract Purpose To prospectively determine the incidence of grade 2 acute genitourinary (GU) toxicity after hypofractionated proton beam therapy (PBT) for localized prostate cancer. Methods The protocol was approved by the institutional review board (IRB). Patients received 51.6 Gy (relative biological effectiveness (RBE)) delivered in 12 fractions over 3 weeks. The primary endpoint was the incidence of grade ≥ 2 acute GU toxicities within 3 months. Neoadjuvant androgen deprivation therapy (ADT) was administered to the intermediate-risk group, and neoadjuvant and adjuvant ADT were administered to high-risk group classified according to the National Comprehensive Cancer Network (NCCN) guideline. Results From March 2021 to June 2024, 100 patients underwent hypofractionated PBT. The incidence of grade 2 acute GU toxicities (urinary frequency) was 8% (95% confidence interval CI 2.6–13.4), meeting the pre-specified continuation criterion. No grade ≥ 3 acute GU toxicities were observed. Furthermore, no grade ≥ 2 acute urinary retention, urinary pain, urinary urgency or hematuria were observed. Univariate analysis preliminarily suggested that compared with the high-risk group patients, the low- and/or intermediate-risk group patients had a higher trend of grade 2 GU toxicities (OR: 0.265 (95% CI 0.066–1.062), P = 0.055). Multivariate regression analysis further confirmed that the high-risk classification was associated with a significantly lower risk grade 2 GU toxicities (OR: 0.023 (95% CI 0.002–0.840), P = 0.042). Additionally, multivariate regression analysis confirmed that benign prostatic hyperplasia (BPH) was an independent influencing factor for grade 2 GU toxicity (OR: 0.040 (95% CI 0.003–0.582), P = 0.018). Conclusions Our results indicate that hypofractionated PBT (51.6 Gy RBE in 12 fractions over 3 weeks) for localized prostate cancer provides acceptable acute GU toxicity rates. Long-term follow-up of the 300-patient expansion cohort is underway to evaluate late toxicities and long-term oncological efficacy.
Yang et al. (2026) studied this question.